Black American males have the highest prostate cancer incidence rate in the world. White Americans have the second highest rate. No environmental risk factors have yet been able to explain the wide interracial and international variation in prostate cancer incidence. The theory that omega-3 fatty acids are protective against prostate cancer arises from the low prostate cancer mortality rates observed in cultures that consume large quantities of fish, such as the Japanese and Eskimos. Support for this theory comes from animal studies in which diets high in omega-3 fatty acids inhibited the progression of implanted human prostate cancer. Conflicting epidemiologic studies of the role of dietary fat in prostate cancer may have resulted from inadequate measurement of exposure to fat and fat components. We will address this issue in our study by adding physiological measurements of fatty acid exposure to dietary questionnaire data. We propose a case-control study to test the theory that omega-3 fatty acids protect against prostate cancer. Cases will be 100 patients with pathologically confirmed, recently diagnosed prostate cancer recruited from the urology clinics of the University of North Carolina Hospitals and the Durham Veterans Administration Medical Center. Controls will be 100 patients with benign prostatic hyperplasia who are free of prostate cancer on pathological examination of the prostate, and frequency matched to the cases on race, age, hospital and study entry date. Subjects will be recruited over a 30 month period, and we expect 40% of the subjects to be black. A research nurse will aspirate subcutaneous fat specimens from the upper arm of the subjects into a Vacutainer tube. The nurse also will obtain venous blood for erythrocyte membranes, and the fatty acids of both adipose tissue and erythrocyte membranes will be analyzed by gas chromatography. We will use adipose tissue and erythrocyte membrane fatty acid composition as estimates of long and short term exposure to fatty acids. A dietary history instrument will serve as an indicator of fatty acid consumption. Data analysis will include crude comparisons of the mean omega-3 fatty acid proportions of cases and controls as well as blacks and whites. Further analyses will explore the differences in mean fatty acid proportions controlled by age, body mass and cholesterol level, and examine the risks of prostate cancer associated with omega-3 fatty acids and omega-6 fatty acids. The proposed study has the potential to advance our understanding of both the epidemiology and etiology of prostate cancer, and the use of tissue fatty acid measurements to determine fatty acid exposure in epidemiologic studies.